JP2004097730A - Medical adhesive composition - Google Patents
Medical adhesive composition Download PDFInfo
- Publication number
- JP2004097730A JP2004097730A JP2002298052A JP2002298052A JP2004097730A JP 2004097730 A JP2004097730 A JP 2004097730A JP 2002298052 A JP2002298052 A JP 2002298052A JP 2002298052 A JP2002298052 A JP 2002298052A JP 2004097730 A JP2004097730 A JP 2004097730A
- Authority
- JP
- Japan
- Prior art keywords
- sensitive adhesive
- pressure
- adhesive composition
- meth
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 44
- 239000000853 adhesive Substances 0.000 title abstract description 23
- 230000001070 adhesive effect Effects 0.000 title abstract description 23
- 239000004014 plasticizer Substances 0.000 claims abstract description 20
- 229920006243 acrylic copolymer Polymers 0.000 claims abstract description 17
- 239000002537 cosmetic Substances 0.000 claims abstract description 12
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims abstract description 8
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims abstract description 4
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 50
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 14
- 239000010410 layer Substances 0.000 claims description 12
- 229920001577 copolymer Polymers 0.000 claims description 8
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 7
- 238000006073 displacement reaction Methods 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000005250 alkyl acrylate group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 17
- 239000012790 adhesive layer Substances 0.000 abstract description 4
- 238000009472 formulation Methods 0.000 abstract description 3
- 239000004615 ingredient Substances 0.000 abstract description 2
- 210000003491 skin Anatomy 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 17
- -1 2-ethylhexyl Chemical group 0.000 description 14
- 206010015150 Erythema Diseases 0.000 description 13
- 231100000321 erythema Toxicity 0.000 description 13
- 238000012360 testing method Methods 0.000 description 12
- 238000010521 absorption reaction Methods 0.000 description 10
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- 238000011156 evaluation Methods 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 206010040880 Skin irritation Diseases 0.000 description 8
- 231100000475 skin irritation Toxicity 0.000 description 8
- 230000036556 skin irritation Effects 0.000 description 8
- 239000000178 monomer Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003431 cross linking reagent Substances 0.000 description 5
- 239000003292 glue Substances 0.000 description 5
- 239000003505 polymerization initiator Substances 0.000 description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 4
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- 239000002904 solvent Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- YIWGJFPJRAEKMK-UHFFFAOYSA-N 1-(2H-benzotriazol-5-yl)-3-methyl-8-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound CN1C(=O)N(c2ccc3n[nH]nc3c2)C2(CCN(CC2)C(=O)c2cnc(NCc3cccc(OC(F)(F)F)c3)nc2)C1=O YIWGJFPJRAEKMK-UHFFFAOYSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229920001342 Bakelite® Polymers 0.000 description 2
- 229920002799 BoPET Polymers 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
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- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000000939 antiparkinson agent Substances 0.000 description 2
- 229940125688 antiparkinson agent Drugs 0.000 description 2
- 239000003907 antipyretic analgesic agent Substances 0.000 description 2
- 210000000467 autonomic pathway Anatomy 0.000 description 2
- 239000004637 bakelite Substances 0.000 description 2
- 238000010382 chemical cross-linking Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000010528 free radical solution polymerization reaction Methods 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 229940125697 hormonal agent Drugs 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 2
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 2
- 229960000991 ketoprofen Drugs 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000004667 medium chain fatty acids Chemical class 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- 239000004081 narcotic agent Substances 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 229960003471 retinol Drugs 0.000 description 2
- 235000020944 retinol Nutrition 0.000 description 2
- 239000011607 retinol Substances 0.000 description 2
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 1
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
- SQUNAWUMZGQQJD-UHFFFAOYSA-N 1-(4-ethylphenyl)-2-methyl-3-(piperidin-1-yl)propan-1-one Chemical compound C1=CC(CC)=CC=C1C(=O)C(C)CN1CCCCC1 SQUNAWUMZGQQJD-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- WYGWHHGCAGTUCH-UHFFFAOYSA-N 2-[(2-cyano-4-methylpentan-2-yl)diazenyl]-2,4-dimethylpentanenitrile Chemical compound CC(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)C WYGWHHGCAGTUCH-UHFFFAOYSA-N 0.000 description 1
- MKMYPTLXLWOUSO-NFQNBQCWSA-N 2-[(2r,6s)-6-[(2s)-2-hydroxy-2-phenylethyl]-1-methylpiperidin-2-yl]-1-phenylethanone;hydrochloride Chemical compound Cl.C1([C@@H](O)C[C@H]2N([C@H](CCC2)CC(=O)C=2C=CC=CC=2)C)=CC=CC=C1 MKMYPTLXLWOUSO-NFQNBQCWSA-N 0.000 description 1
- FEDJGPQLLNQAIY-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)oxy]acetic acid Chemical compound OC(=O)COC=1C=CC(=O)NN=1 FEDJGPQLLNQAIY-UHFFFAOYSA-N 0.000 description 1
- NFIHXTUNNGIYRF-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate Chemical compound CCCCCCCCCC(=O)OCC(C)OC(=O)CCCCCCCCC NFIHXTUNNGIYRF-UHFFFAOYSA-N 0.000 description 1
- UPZFLZYXYGBAPL-UHFFFAOYSA-N 2-ethyl-2-methyl-1,3-dioxolane Chemical compound CCC1(C)OCCO1 UPZFLZYXYGBAPL-UHFFFAOYSA-N 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- AKUVRZKNLXYTJX-UHFFFAOYSA-N 3-benzylazetidine Chemical compound C=1C=CC=CC=1CC1CNC1 AKUVRZKNLXYTJX-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 1
- TZZAKSLHHIJRLL-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzamide Chemical compound COC1=CC(C(N)=O)=CC=C1O TZZAKSLHHIJRLL-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
【０００１】
【産業上の利用分野】本発明は、粘着性に優れ、刺激性の少ない粘着剤組成物、及び、それを用いた医療用、化粧用貼付剤に関する。
【０００２】
【従来の技術】従来、疾患の治療においては、薬物の経口投与や注射投与によるのが一般的であったが、比較的最近薬剤を体内に経皮的に投与する方法が用いられるようになった。
経皮吸収製剤の特性としては、皮膚に貼付後、一般に２４〜４８時間程度確実に密着して、所要の薬物量が吸収されることが必要であり、発汗時、入浴時にも密着し剥離しないことが必要である。また、剥離時は痛くない程度の剥離力で引き剥がせることも必要であり、粘着力が必要以上に強いと剥離時に毛むしりや角質剥離が起きたり、皮膚の引っ張りによる機械的皮膚刺激を生じる。その結果、紅斑が発生し、ひどい場合には痂皮形成や浮腫形成を伴ない、これが剥離後も数日間続く場合もあるので、このような不都合をできるだけ少なくする必要がある。また、経皮吸収製剤を皮膚から剥離した後、皮膚面に粘着剤が残存しないことも要求される。
【０００３】
特開昭６１−１００５２０号公報には、２−エチルヘキシルアクリレート４５モル％以上、ビニルピロリドン２０〜５５モル％及びエステル部分の炭素数が３〜１２のアクリル酸エステル３５モル％以下からなり、さらに多官能性モノマーを全モノマー重量の０．００５〜０．５重量％含む粘着剤が提案されている。しかしこの粘着剤を用いた経皮吸収製剤は上記の特性を有してはいるが、薬物放出性を向上させるために軟化剤、可塑剤等を添加した場合、凝集力が不足し糊残りが生じるという欠点があった。従って、優れた貼付剤を獲得するためには、特に糊残りの問題を解決することが必要である。
【０００４】
経皮吸収製剤においては、粘着剤層の適当な凝集力を確保し、糊残りを無くすため、粘着剤を架橋する方法が用いられてきた。例えば、粘着剤自体を架橋剤等によって微架橋する方法や、粘着剤層を形成した後に金属イオン架橋、ウレタン架橋、エポキシ架橋、メラミン架橋又は過酸化物若しくは電子線照射によるラジカル反応で架橋する方法が知られている。しかしながら、上記のような架橋法を適用すると、凝集力は向上するが粘着剤の硬化により粘着性は低下し、貼付性が悪くなるという欠点があった。
【０００５】
また、上記架橋粘着剤の改良として、多量の可塑剤を含有せしめて架橋させる方法が提案されている。例えば、特許２７００８３５、特許３０１４１８８、等。しかし、この経皮吸収製剤の場合、粘着剤層の保型性を高めることができるが、皮膚への粘着力と、粘着剤の凝集力をバランスさせた製剤設計が困難である、あるいは架橋剤と薬剤が反応して薬剤安定性が悪化しがちである、等の欠点を有していた。
【０００６】
【発明が解決しようとする課題】本発明は、上記に鑑み、粘着力と凝集力のバランスがとれ、皮膚刺激性の少ない粘着剤組成物、及び、それを用いた医療用、化粧用粘着シートを提供することを目的とする。
【０００７】
【課題を解決するための手段】本発明の要旨は、アクリル系共重合体１００重量部、可塑剤２０−６０部よりなる粘着剤組成物であって、該アクリル系共重合体がアクリル酸アルキルエステルと（メタ）アクリル酸と（メタ）アクリル酸ヒドロキシエチルとビニルピロリドンとの共重合体であることを特徴とする医用粘着剤組成物に存する。
【０００８】
上記アクリル系共重合体には粘着性付与のために（メタ）アクリル酸アルキルエステルが４０−７０重量％必要であり、例えば（メタ）アクリル酸ブチル、（メタ）アクリル酸イソブチル、アクリル酸ヘキシル、アクリル酸オクチル、（メタ）アクリルド酸２−エチルヘキシル、（メタ）アクリル酸イソオクチル、（メタ）アクリル酸ドデシル等が挙げられ、これらは単独で用いてもよいし、併用されてもよい。
【０００９】
上記アクリル系共重合体には、粘着剤の凝集力を高める、あるいは薬物、化粧品原料の粘着剤中への溶解度を高める目的で、１０−２５重量％の（好ましくは１５−２０％の）２−ビニルピロリドン、１０−３５％（好ましくは１５−３０％）の（メタ）アクリル酸ヒドロキシエチル、０．５−７．０％（好ましくは１．０−５％）の（メタ）アクリル酸を含むことが必要である。発明者は、このような共重合体が架橋剤による化学架橋、イオン架橋をさせなくとも可塑剤を該アクリル系共重合体１００重量部に対して、２０−６０部添加した状態で十分な凝集力を有し皮膚に優しい医用粘着剤となることを見出し本発明を完成するに至った。
【００１０】
本発明におけるアクリル系共重合体を特徴とする粘着剤においてはアクリルアルキルエステル以外に無架橋であっても分子間相互作用によって強い相互作用を生じ可塑剤添加時においても適度の凝集力を有するために、２−ビニルピロリドン、（メタ）アクリル酸ヒドロキシエチル、（メタ）アクリル酸の３種を含むことが必要である。２−ビニルピロリドンと（メタ）アクリル酸ヒドロキシエチルとが水素結合による分子間相互作用と、また（メタ）アクリル酸はカルボキシル基同士の会合による分子間相互作用とによって高分子間の擬似架橋が生じるものと思慮される。
【００１１】
２−ビニルピロリドンの上記アクリル系共重合体中含量が１０％以下では可塑剤を加えた組成物における凝集力が少なすぎて貼付後の剥離時に糊残りする、また２５％以上では重合体は硬くなり、可塑剤を加えた組成物における粘着性が不足する。（メタ）アクリル酸ヒドロキシエチルの上記アクリル系共重合体中含量が１０％以下では可塑剤を加えた組成物における凝集力が少なすぎて貼付後の剥離時に糊残りする、また２５％以上では重合体は硬くなり、可塑剤を加えた組成物における粘着性が不足する。（メタ）アクリル酸の上記アクリル系共重合体中含量が０．５％以下では可塑剤を加えた組成物における凝集力が少なすぎて貼付後の剥離時に糊残りする、また７％以上では重合体は粘着剤自身の極性が高くなりすぎて可塑剤をブリードしやすい。
【００１２】
上記アクリル系共重合体を調製するには、通常、重合開始剤の存在下で所要モノマーの溶液重合を行う。ただし、重合形態はこれに限定されない。溶液重合を行う場合、例えば、所要モノマーの所定量に、酢酸エチル又はその他の一般的な重合溶媒を加え、攪拌装置及び冷却還流装置を備えた反応容器中でアゾビス系、過酸化物系等の重合開始剤の存在下、窒素雰囲気で７０〜９０℃、８〜４０時間反応させればよい。なお、上記モノマー及び溶媒は一括投入してもよいし、適宜分割投入してもよい。重合開始剤は反応の進行状況に応じて、適宜分割投入するのが望ましい。
【００１３】
上記アゾビス系重合開始剤としては、例えば、２，２′−アゾビス−イソ−ブチロニトリル、１，１′−アゾビス（シクロヘキサン−１−カルボニトリル）、２，２′−アゾビス−（２，４−ジメチルバレロニトリル）等が挙げられ、上記過酸化物系重合開始剤としては、例えば、過酸化ラウロイル、過酸化ベンゾイル、ジ（ｔｅｒｔ−ブチル）パーオキサイド等が挙げられる。
【００１４】
本発明の医用粘着剤組成物を製造するには上記アクリル系共重合体に、可塑剤を添加する。
添加量はアクリル系共重合体１００重量部に対し２０−５０部であり、好ましくは３０−４０部である。添加量は２０部より少ないと本発明の目的である皮膚刺激性が少ない貼付剤となりにくく、５０部より多いと粘着剤組成物の凝集力が不足し糊残りしがちである。
【００１５】
上記可塑剤としては、例えば、オクタン酸セチル、ラウリン酸ヘキシル、ミリスチン酸イソプロピル、パルミチン酸イソプロピル、ステアリン酸ブチル、乳酸ミリスチル等の一価アルコールの脂肪酸エステル；アジピン酸ジオクチル、セバシン酸ジエチル、セバシン酸ジオクチル、コハク酸ジオクチル等の二塩基酸エステル；ジカプリン酸プロピレングリコール、トリオクタン酸グリセリル、トリ（オクタン酸／デカン酸）グリセリル、中鎖脂肪酸トリグリセリド等の多価アルコール等の脂肪酸エステル、等が挙げられ、特にミリスチン酸イソプロピル、パルミチン酸イソプロピル、セバシン酸ジエチル、中鎖脂肪酸トリグリセリド等の脂肪酸エステル、が好適に使用される。
【００１６】
従来型アクリル系粘着剤組成物と本発明の粘着剤組成物との物性的違いはクリープ挙動において区別される。すなわち、ポリエチレンテレフタレートを支持体として、アクリル系共重合体１００部に可塑剤４０部を添加した粘着剤組成物シート（厚さ８０−１２０ミクロン）を幅１ｃｍに切断してテープ状とし、２５℃においてベークライト板へ１ｃｍｘ１ｃｍの接着面積で荷重５００ｇのローラーを往復させて密着させた後、板を垂直にして３ｇの荷重をかけて放置し、２分間後のずれ変形距離〔ずれ変形移動距離（３ｇ、２分）〕を測定する。従来型アクリル系粘着剤からなる組成物の大部分はは凝集力不足のためずれ変形距離は大きく１ｍｍ以上となる。本発明の粘着剤組成物のずれ変形距離は０．５ｍｍ以下である。組成物の凝集力が大きくても、可塑剤を高濃度に含浸不可能な場合は可塑剤の表面ブリードが起こる場合、また硬くなって粘着力が低下する場合、いずれの場合もずり変形距離は大きく１ｍｍ以上となる。
【００１７】
また化学架橋品対しては皮膚貼付性の向上である。化学架橋品は皮膚貼付時に皮膚の動きに追随できず粘着テープは剥がれることが多い、しかしながら本発明品は皮膚の変形に対して粘着着剤の塑性変形によって追随できるので皮膚貼付性ははるかに優れるものである。
【００１８】
本発明は、支持体の片面に、本発明の上記アクリル系粘着剤組成物層を積層して構成するものであるが、さらに皮膚有価物を添加して経皮吸収製剤、貼付用化粧品とすることができる。本発明品の第一の特徴は適度の粘着性に起因する皮膚刺激性の低減である。第２に、化学架橋剤を用いないので反応性に富む化学架橋剤が薬物と反応して薬物を分解させる事も無い。
【００１９】
上記支持体は、薬物が不透過性又は難透過性のものであって柔軟なものが好ましく、例えば、ポリエチレン、ポリプロピレン、エチレン−メチルアクリレート共重合体、エチレン−酢酸ビニル共重合体、エチレン−酢酸ビニル−一酸化炭素共重合体、エチレン−ブチルアクリレート−一酸化炭素共重合体、ポリ塩化ビニリデン、ポリウレタン、ナイロン、ポリエチレンテレフタレート、ポリブチレンテレフタレート等の樹脂フィルム；アルミニウムシート等が挙げられ、これらの積層シートであってもよく、織布や不織布と積層されていてもよい。また、粘着剤層との接着性を高める目的で、コロナ処理、プラズマ放電処理等の表面処理を施したり、アンカー剤によりアンカーコート処理を施してもよい。
【００２０】
上記粘着剤組成物に含有させる皮膚有価物としての薬物は、経皮的に生体膜を透過しうるものであれば特に限定されず、例えば、解熱鎮痛消炎剤、ステロイド系抗炎症剤、血管拡張剤、不整脈用剤、血圧降下剤、局所麻酔剤、ホルモン剤、抗ヒスタミン剤、全身麻酔剤、睡眠鎮痛剤、抗癲癇剤、精神神経用剤、骨格筋弛緩剤、自立神経用剤、抗パーキンソン剤、利尿剤、血管収縮剤、呼吸促進剤、麻薬等が挙げられる。
【００２１】
上記解熱鎮痛消炎剤としては、例えば、イブプロフェン、フルルピプロフェン、ケトプロフェン、等が挙げられ上記ステロイド系抗炎症剤としては、例えば、ヒドロコルチゾン、トリアムシノロン、プレドニゾロン等が挙げられる。上記血管拡張剤としては、例えば、塩酸ジルチアゼム、硝酸イソソルビド、等が挙げられる。上記不整脈用剤としては、例えば、塩酸プロカインアミド、塩酸メキシレチン等が挙げられる。上記血圧降下剤としては、例えば、塩酸クロニジン、塩酸ブニトロロール、カプトプリル、等が挙げられる。上記局所麻酔剤としては、例えば、塩酸テトラカイン、塩酸プロピトカイン等が挙げられる。上記ホルモン剤としては、例えば、プロピルチオウラシル、エストラジオール、エストリオール、プロゲステロン等が挙げられる。上記抗ヒスタミン剤としては、例えば、塩酸ジフェンヒドラミン、マレイン酸クロルフェニラミン、等が挙げられる。
【００２２】
上記全身麻酔剤としては、例えば、ペントバルビタールナトリウム等が挙げられる。上記睡眠・鎮痛剤としては、例えば、アモバルビタール、フェノバルビタール等が挙げられる。
上記抗癲癇剤としては、例えば、フェニトインナトリウム等が例示される。上記精神神経用剤としては、例えば、塩酸クロルプロマジン、塩酸イミプラミン、クロルジアゼポキシド、ジアゼパム等が挙げられる。上記骨格筋弛緩剤としては、例えば、塩酸スキサメトニウム、塩酸エペリゾン等が挙げられる。上記自立神経用剤としては、例えば、臭化ネオスチグミン、塩化ベタネコール等が挙げられる。上記抗パーキンソン剤としては、例えば、塩酸アマンタジン等が挙げられる。上記利尿剤としては、例えば、ヒドロフルメチアジド、イソソルビド、フロセミド等が挙げられる。上記血管収縮剤としては、例えば、塩酸フェニレフリン等が挙げられる。上記呼吸促進剤としては、例えば、塩酸ロベリン、ジモルホラミン、塩酸ナロキソン等が挙げられる。上記麻薬としては、例えば、塩酸モルヒネ、塩酸コカイン、塩酸ペチジン等が挙げられる。
【００２３】
皮膚有価物としての化粧品原料の具体例を下記にリストするとパルミチン酸アスコルビル、コウジ酸、ルシノール、トラネキサム酸、油用性甘草エキス、ビタミンＡ誘導体等の美白成分、レチノール、レチノイン酸、酢酸レチノール、パルミチン酸レチノール、等の抗しわ成分、酢酸トコフェロール、カプサイン、ノリル酸バニリルアミド、等の血行促進成分、ラズベリーケトン、月見草エキス、海草エキス、等のダイエット成分、イソプロピルメチルフェノール、感光素、酸化亜鉛、等の抗菌成分、ビタミンＤ２、ビタミンＤ３、ビタミンＫ、等のビタミン類、等が特に好適に含有される。
【００２４】
上記薬物、化粧品原料の含有量は、種類、使用目的に応じて適宜決定されるが、少なくなると有効性が低下し、多くなると粘着性が低下することから、粘着剤層中０．０１〜５０重量％が好ましい。薬物が粘着剤層中で過飽和状態で存在したり、結晶が析出した状態で存在していても特に支障はない。また、薬物を吸収促進剤とともにカプセル化したり、薬物貯蔵層を設けてもよい。
【００２５】
本発明の粘着剤層の厚みは、特に限定されるものではないが、薄くなると皮膚有価物を多量に添加せねばならず、粘着力が低下し、厚くなると支持体付近の粘着剤中に存在する皮膚有価物が粘着剤層表面に拡散しにくくなり、薬物放出率が低下するので、１０−２００μｍが好ましい。
【００２６】
本発明の経皮吸収製剤の製造には、従来公知の粘着テープの製造方法が使用でき、例えば、溶剤塗工法では、粘着剤、可塑剤、皮膚有価物、を所定量、酢酸エチル等の溶液に溶解又は分散させ、得られた液を支持体上に塗布・乾燥する方法、剥離紙上に塗布・乾燥した後支持体上に転写する方法等が好適に使用される。
【００２７】
【実施例】以下に実施例を掲げて、本発明をさらに詳しく説明するが、本発明はこれらに限定されるものではない。なお、以下「部」とあるのは「重量部」を意味する。
【００２８】
アクリル系共重合体の合成
【００２９】
実施例１
アクリル酸２−エチルヘキシル３２０部、ビニルピロリドン８０部、アクリル酸ヒドロキシエチル８０部、アクリル酸２０部、及び酢酸エチル３００部を攪拌装置及び還流冷却装置付きセパラブルフラスコに供給し、攪拌及び窒素置換しながら７５℃に昇温した。アゾビスイソブリロニトリル２部を酢酸エチル２０部に溶解した溶液を４分割し、その１をセパラブルフラスコに添加し、重合を開始した。残部の３を反応開始後２時間目から２時間間隔で添加し、添加終了後、さらに６時間反応させた。なお、粘度調節のため反応開始後、２時間毎に酢酸エチルを５０部づつ４回添加した。反応終了後、冷却し、次いで酢酸エチルを追加して固形分濃度３０重量％、粘度１．２×１０４ｃｐｓの粘着剤溶液を得た。
【００３０】
実施例２−実施例７、比較例１−９
実施例１におけるモノマー組成を変更した以外は実施例１と同様に重合した。モノマー組成と粘度を第１表に示す。
試験用シートの作成とずれ変形移動距離の測定
実施例１−７，比較例１−９によって得られた粘着剤溶液に、可塑剤を加えて、液全体をディゾルバーにて均一に攪拌し、混合液を得た。得られた混合液をシリコン処理した厚さ３５μｍのＰＥＴフィルム上に乾燥後の粘着剤層の厚みが１００μｍになるように塗布し、乾燥させ、次いで厚さ３５μｍのＰＥＴフィルム上に上記粘着剤層をラミネートして皮膚用粘着シートを得た。次いで、作成したシートを幅１ｃｍに切断してテープ状とし、２５℃においてベークライト板へ１ｃｍｘ１ｃｍの接着面積で荷重５００ｇのローラー往復させて密着させた後板を垂直にしてずれ変形距離（３ｇ、２分）を測定した。
【００３２】
以下の表２には、上記のようにして作成、測定した皮膚用粘着シートの組成、ずれ移動距離測定結果を示す。
皮膚刺激試験及び貼付性試験
【００３４】
［皮膚刺激試験］
上記により得られた試験シートについて、以下の評価を行い、結果を表５に示した。
成人男子５人の上腕部に各試験シート（２０ｃｍ２）を貼付し、２４時間後に剥離した。剥離して１時間後の皮膚の状態を目視で観察して、下記評価基準により評価し、５人の評点の総和の平均値を指数とした。
（評価基準）
０：紅斑なし、１：かろうじて識別できる程度のごく軽度の紅斑、２：明らかな紅斑３：中程度の紅斑、４：深紅色の強い紅斑
【００３５】
［貼付性］
成人男子５人の上腕部に各経皮吸収製剤を貼付し、２４時間後に剥離した。剥離直前の皮膚上のシートの貼付状態を目視で観察して、下記評価基準により評価した。
（評価基準）
○：ほぼ全員完全に貼付、□：１〜３人に部分的剥離あり、×：４〜５人に剥離あり
【００３６】
［のり残り試験］
成人男子５人の上腕部に各経皮吸収製剤を貼付し、２４時間後に剥離した。剥離直後の皮膚の状態を目視で観察して、下記評価基準により評価した。
（評価基準）
○：ほぼ全員完全に糊残りなし、□：１〜３人に部分的糊残りあり、×：４〜５人に糊残りあり
経皮吸収製剤、化粧品パッチの製造と評価
実施例８−１２、比較例１９、２０、を構成成分とするアクリルアルキルエステル組成物及び皮膚有価物を表６に示す配合とした以外は上記度同様にして医薬品パッチ、化粧品パッチを作成し、評価した。結果を表６に示す。表中、Ｈはインドメタシンを、Ｋはケトプロフェンを、ＥはビタミンＥを、それぞれ表わす。
【００３８】
刺激性
日本白色種のウサギの脱毛した背部にテープ剤の試験片（面積１６ｃｍ２）を貼付し、２４時間後、これを剥離し、剥離直後及び剥離１時間後の皮膚の紅斑状態を目視で観察した。
なお、本試験において浮腫及び痂皮の形成は認められなかった。繰り返し回数は各製剤毎に４回とした。紅斑の程度は下記の０〜４の５段階の判定基準で評価した。
０：紅斑なし、１：かろうじて識別できるごく軽度の紅斑、２：明らかな紅斑、３：中程度の紅斑、４：深紅色の強い紅斑。
各回における評点の総和を繰り返し回数４で割った平均値を各々のテープ製剤の皮膚刺激指数とした。
【００３９】
貼付性
上記刺激性の試験と同じ操作で、ウサギの皮膚にテープ製剤を２４時間貼付し、剥離直前の貼付性の有無を目視で観察した。繰り返し回数は各製剤毎に４回とした。評価基準は下記の通りである。
０：製剤剥離なし１：一部に剥離を認める２：明らかに剥離を認める
平均値（評価点の総和を繰り返し回数４で割った値）を各製剤の貼付性指数とした。
【発明の効果】本発明の医用粘着剤組成物及びそれを用いた経皮吸収製剤、化粧品用シートは、上述の通りの構成であるので、粘着力と凝集力のバランスがとれた良好な貼付性を示すため、剥がす際に、糊残りがなく、皮膚表面の角質層の損傷、毛むしり等の機械的刺激等による皮膚刺激を低減できる。[0001]
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pressure-sensitive adhesive composition having excellent tackiness and little irritation, and a medical or cosmetic patch using the same.
[0002]
2. Description of the Related Art Conventionally, in the treatment of diseases, oral administration or injection administration of a drug has generally been used. However, relatively recently, a method of transdermally administering a drug into the body has been used. Was.
As a characteristic of a transdermal absorption preparation, it is necessary that, after being applied to the skin, it generally adheres firmly for about 24 to 48 hours and absorbs a required amount of the drug. It is necessary. It is also necessary to be able to peel off with a peeling force that is not painful at the time of peeling, and if the adhesive force is too strong, scalp and exfoliation will occur at peeling, and mechanical skin irritation due to pulling of the skin will occur . As a result, erythema occurs, which is accompanied by crusting and edema formation in severe cases, which may continue for several days after detachment. Therefore, it is necessary to minimize such inconvenience. Further, it is also required that the adhesive does not remain on the skin surface after the transdermal absorption preparation is peeled from the skin.
[0003]
JP-A-61-100520 discloses that 2-ethylhexyl acrylate is composed of 45 mol% or more, vinylpyrrolidone 20 to 55 mol%, and an acrylate having 3 to 12 carbon atoms in an ester portion of 35 mol% or less. An adhesive containing a functional monomer in an amount of 0.005 to 0.5% by weight of the total monomer weight has been proposed. However, although the percutaneous absorption preparation using this pressure-sensitive adhesive has the above characteristics, when a softener, a plasticizer, etc. are added to improve the drug release property, the cohesive force is insufficient and the adhesive residue remains. There was a disadvantage that it occurred. Therefore, in order to obtain an excellent patch, it is particularly necessary to solve the problem of adhesive residue.
[0004]
In percutaneous absorption preparations, a method of cross-linking an adhesive has been used in order to secure an appropriate cohesive force of the adhesive layer and eliminate adhesive residue. For example, a method of micro-crosslinking the pressure-sensitive adhesive itself with a cross-linking agent or a method of forming a pressure-sensitive adhesive layer and then cross-linking by metal ion crosslinking, urethane crosslinking, epoxy crosslinking, melamine crosslinking, or radical reaction by peroxide or electron beam irradiation. It has been known. However, when the cross-linking method as described above is applied, there is a disadvantage that the cohesive strength is improved, but the tackiness is reduced due to the curing of the pressure-sensitive adhesive, and the sticking property is deteriorated.
[0005]
Further, as a method for improving the above-mentioned crosslinked pressure-sensitive adhesive, there has been proposed a method in which a large amount of a plasticizer is contained for crosslinking. For example, Patents 2700835 and 3014188. However, in the case of this transdermal absorption preparation, although the shape retention of the pressure-sensitive adhesive layer can be enhanced, it is difficult to design a preparation that balances the adhesion to the skin and the cohesion of the pressure-sensitive adhesive, or a cross-linking agent. And the drug tends to react to deteriorate the drug stability.
[0006]
DISCLOSURE OF THE INVENTION In view of the above, the present invention provides a pressure-sensitive adhesive composition which has a good balance between adhesive force and cohesive force and has low skin irritation, and a medical or cosmetic pressure-sensitive adhesive sheet using the same. The purpose is to provide.
[0007]
The gist of the present invention is to provide a pressure-sensitive adhesive composition comprising 100 parts by weight of an acrylic copolymer and 20 to 60 parts of a plasticizer, wherein the acrylic copolymer is an alkyl acrylate. A medical pressure-sensitive adhesive composition comprising a copolymer of an ester, (meth) acrylic acid, hydroxyethyl (meth) acrylate and vinylpyrrolidone.
[0008]
The acrylic copolymer requires 40 to 70% by weight of an alkyl (meth) acrylate for imparting tackiness, such as butyl (meth) acrylate, isobutyl (meth) acrylate, hexyl acrylate, Examples thereof include octyl acrylate, 2-ethylhexyl (meth) acrylate, isooctyl (meth) acrylate, and dodecyl (meth) acrylate. These may be used alone or in combination.
[0009]
The acrylic copolymer contains 10 to 25% by weight (preferably 15 to 20%) of 2 to increase the cohesive strength of the pressure-sensitive adhesive or to increase the solubility of a drug or cosmetic raw material in the pressure-sensitive adhesive. Vinylpyrrolidone, 10-35% (preferably 15-30%) hydroxyethyl (meth) acrylate, 0.5-7.0% (preferably 1.0-5%) (meth) acrylic acid It is necessary to include. The inventor has found that such a copolymer does not undergo chemical or ionic cross-linking by a cross-linking agent and that a sufficient amount of coagulation can be obtained in a state where 20 to 60 parts of a plasticizer is added to 100 parts by weight of the acrylic copolymer. The present inventors have found that it is a medical pressure-sensitive adhesive which has power and is gentle on the skin, and has completed the present invention.
[0010]
In the pressure-sensitive adhesive characterized by the acrylic copolymer in the present invention, in addition to the acrylic alkyl ester, even if non-crosslinked, a strong interaction occurs due to intermolecular interaction and has an appropriate cohesive force even when a plasticizer is added. Needs to contain three kinds of 2-vinylpyrrolidone, hydroxyethyl (meth) acrylate, and (meth) acrylic acid. Pseudocrosslinking between polymers occurs due to the intermolecular interaction between 2-vinylpyrrolidone and hydroxyethyl (meth) acrylate due to hydrogen bonding, and the intermolecular interaction of (meth) acrylic acid due to association between carboxyl groups. Is considered.
[0011]
When the content of 2-vinylpyrrolidone in the acrylic copolymer is 10% or less, the cohesive force of the composition containing the plasticizer is too small to leave glue when peeled off after application. When the content is 25% or more, the polymer is hard. And the tackiness of the composition to which the plasticizer is added is insufficient. If the content of hydroxyethyl (meth) acrylate in the acrylic copolymer is 10% or less, the cohesive force of the composition to which the plasticizer is added is too small, and the adhesive remains when peeled off after application. The coalescence becomes hard and the tackiness of the composition with the added plasticizer is insufficient. When the content of the (meth) acrylic acid in the acrylic copolymer is 0.5% or less, the cohesive force of the composition to which the plasticizer is added is too small, and the adhesive remains when peeled off after application. In the coalescing, the polarity of the pressure-sensitive adhesive itself becomes too high, and the plasticizer easily bleeds.
[0012]
In order to prepare the acrylic copolymer, solution polymerization of a required monomer is usually performed in the presence of a polymerization initiator. However, the polymerization form is not limited to this. In the case of performing solution polymerization, for example, to a predetermined amount of a required monomer, ethyl acetate or other general polymerization solvent is added, and an azobis-based, peroxide-based The reaction may be carried out in a nitrogen atmosphere at 70 to 90 ° C. for 8 to 40 hours in the presence of a polymerization initiator. The above-mentioned monomer and solvent may be charged at once or may be dividedly charged as appropriate. It is desirable that the polymerization initiator be appropriately divided and charged according to the progress of the reaction.
[0013]
Examples of the azobis-based polymerization initiator include, for example, 2,2'-azobis-iso-butyronitrile, 1,1'-azobis (cyclohexane-1-carbonitrile), 2,2'-azobis- (2,4-dimethyl Valeronitrile). Examples of the peroxide-based polymerization initiator include lauroyl peroxide, benzoyl peroxide, di (tert-butyl) peroxide, and the like.
[0014]
In order to produce the medical pressure-sensitive adhesive composition of the present invention, a plasticizer is added to the acrylic copolymer.
The addition amount is 20 to 50 parts, preferably 30 to 40 parts, per 100 parts by weight of the acrylic copolymer. If the amount is less than 20 parts, it is difficult to obtain a patch with less skin irritation, which is the object of the present invention, and if it is more than 50 parts, the cohesive force of the pressure-sensitive adhesive composition is insufficient and adhesive tends to remain.
[0015]
Examples of the plasticizer include fatty acid esters of monohydric alcohols such as cetyl octanoate, hexyl laurate, isopropyl myristate, isopropyl palmitate, butyl stearate, and myristyl lactate; dioctyl adipate, diethyl sebacate, and dioctyl sebacate. And dibasic acid esters such as dioctyl succinate; fatty acid esters such as polyhydric alcohols such as propylene glycol dicaprate, glyceryl trioctanoate, glyceryl tri (octanoate / decanoate), and triglycerides of medium-chain fatty acids; Fatty acid esters such as isopropyl myristate, isopropyl palmitate, diethyl sebacate, and medium-chain fatty acid triglyceride are preferably used.
[0016]
The physical property difference between the conventional acrylic pressure-sensitive adhesive composition and the pressure-sensitive adhesive composition of the present invention is distinguished by the creep behavior. That is, an adhesive composition sheet (thickness: 80 to 120 μm) obtained by adding 40 parts of a plasticizer to 100 parts of an acrylic copolymer using polyethylene terephthalate as a support is cut into a width of 1 cm to form a tape, and the temperature is 25 ° C. , A roller with a load of 500 g was reciprocated and adhered to the bakelite plate with an adhesion area of 1 cm x 1 cm, and then the plate was allowed to stand vertically with a load of 3 g, and the displacement distance after 2 minutes [shift displacement distance (3 g) , 2 minutes)]. Most of the compositions composed of conventional acrylic pressure-sensitive adhesives have a large shear deformation distance of 1 mm or more due to insufficient cohesive force. The shear deformation distance of the pressure-sensitive adhesive composition of the present invention is 0.5 mm or less. Even if the cohesive force of the composition is large, if the plasticizer cannot be impregnated at a high concentration, the surface bleeding of the plasticizer occurs, or if the composition becomes hard and the adhesive strength decreases, the shear deformation distance is reduced in any case. It is 1 mm or more.
[0017]
It is also an improvement in skin sticking properties for chemically crosslinked products. The chemically cross-linked product cannot follow the movement of the skin at the time of application to the skin and the adhesive tape often peels off.However, the product of the present invention can follow the deformation of the skin by the plastic deformation of the adhesive, so the skin application property is much better. Things.
[0018]
The present invention is constituted by laminating the above-mentioned acrylic pressure-sensitive adhesive composition layer of the present invention on one surface of a support, and further adding skin valuables to obtain a transdermal absorption preparation and a cosmetic for application. be able to. The first feature of the product of the present invention is a reduction in skin irritation due to moderate tackiness. Second, since no chemical cross-linking agent is used, the highly reactive chemical cross-linking agent does not react with the drug to decompose the drug.
[0019]
The support is preferably a material in which the drug is impermeable or hardly permeable and is flexible. For example, polyethylene, polypropylene, ethylene-methyl acrylate copolymer, ethylene-vinyl acetate copolymer, ethylene-acetic acid are preferable. Resin films such as vinyl-carbon monoxide copolymer, ethylene-butyl acrylate-carbon monoxide copolymer, polyvinylidene chloride, polyurethane, nylon, polyethylene terephthalate, and polybutylene terephthalate; aluminum sheets and the like; It may be a sheet, or may be laminated with a woven or nonwoven fabric. Further, for the purpose of enhancing the adhesiveness to the pressure-sensitive adhesive layer, a surface treatment such as a corona treatment or a plasma discharge treatment may be performed, or an anchor coating treatment may be performed with an anchor agent.
[0020]
The drug as a skin valuable contained in the pressure-sensitive adhesive composition is not particularly limited as long as it can penetrate a biological membrane percutaneously, and includes, for example, antipyretic analgesic and anti-inflammatory agent, steroidal anti-inflammatory agent, and vasodilator. Agents, antiarrhythmic agents, antihypertensive agents, local anesthetics, hormonal agents, antihistamines, general anesthetics, sleep analgesics, antiepileptics, mental nerve agents, skeletal muscle relaxants, autonomic nerve agents, antiparkinson agents, Diuretics, vasoconstrictors, respiratory stimulants, narcotics and the like.
[0021]
Examples of the antipyretic analgesic / inflammatory agent include ibuprofen, flurpiprofen, ketoprofen and the like, and examples of the steroidal anti-inflammatory agent include hydrocortisone, triamcinolone, prednisolone and the like. Examples of the vasodilator include diltiazem hydrochloride, isosorbide dinitrate, and the like. Examples of the arrhythmic agent include procainamide hydrochloride, mexiletine hydrochloride and the like. Examples of the antihypertensive include clonidine hydrochloride, bunitrolol hydrochloride, captopril, and the like. Examples of the local anesthetic include tetracaine hydrochloride, propitocaine hydrochloride and the like. Examples of the hormonal agent include propylthiouracil, estradiol, estriol, and progesterone. Examples of the antihistamine include diphenhydramine hydrochloride, chlorpheniramine maleate, and the like.
[0022]
Examples of the general anesthetic include sodium pentobarbital and the like. Examples of the sleep / analgesic include amobarbital and phenobarbital.
Examples of the antiepileptic agent include phenytoin sodium and the like. Examples of the above agents for psychiatric nerves include chlorpromazine hydrochloride, imipramine hydrochloride, chlordiazepoxide, diazepam and the like. Examples of the skeletal muscle relaxant include suxamethonium hydrochloride, eperisone hydrochloride and the like. Examples of the agent for autonomic nerves include neostigmine bromide, bethanechol chloride and the like. Examples of the anti-Parkinson agent include amantadine hydrochloride and the like. Examples of the diuretic include hydroflumethiazide, isosorbide, furosemide and the like. Examples of the vasoconstrictor include phenylephrine hydrochloride and the like. Examples of the respiratory enhancer include lobeline hydrochloride, dimorpholamine, naloxone hydrochloride and the like. Examples of the narcotics include morphine hydrochloride, cocaine hydrochloride, pethidine hydrochloride and the like.
[0023]
Specific examples of cosmetic raw materials as skin valuables are listed below. Whitening ingredients such as ascorbyl palmitate, kojic acid, lucinol, tranexamic acid, licorice extract for oils, vitamin A derivatives, retinol, retinoic acid, retinol acetate, palmitin Anti-wrinkle components such as acid retinol, etc., blood circulation promoting components such as tocopherol acetate, capsin, vanillyl amide, etc., diet components such as raspberry ketone, evening primrose extract, seaweed extract, etc., and antibacterial agents such as isopropylmethylphenol, photosensitizer, zinc oxide, etc. Components, vitamins such as vitamin D 2 , vitamin D 3 , vitamin K, and the like are particularly preferably contained.
[0024]
The content of the above drug and cosmetic ingredients is appropriately determined depending on the type and purpose of use. However, when the content is small, the effectiveness is reduced, and when the content is large, the adhesiveness is reduced. % By weight is preferred. There is no particular problem even if the drug exists in the pressure-sensitive adhesive layer in a supersaturated state or in a state where crystals are precipitated. Further, the drug may be encapsulated together with the absorption enhancer, or a drug storage layer may be provided.
[0025]
The thickness of the pressure-sensitive adhesive layer of the present invention is not particularly limited. However, when the pressure-sensitive adhesive layer is thin, a large amount of skin valuables must be added, the adhesive strength is reduced, and when the pressure-sensitive adhesive layer is thick, it is present in the pressure-sensitive adhesive near the support. 10 to 200 μm is preferable, since the skin valuables to be dispersed hardly diffuse to the surface of the pressure-sensitive adhesive layer, and the drug release rate decreases.
[0026]
For the production of the percutaneously absorbable preparation of the present invention, a conventionally known method for producing a pressure-sensitive adhesive tape can be used.For example, in a solvent coating method, a predetermined amount of a pressure-sensitive adhesive, a plasticizer, a skin valuable, a solution of ethyl acetate or the like. A method of dissolving or dispersing the resultant in a liquid and applying and drying the obtained liquid on a support, a method of applying and drying on a release paper and then transferring it to the support, and the like are suitably used.
[0027]
EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto. Hereinafter, “parts” means “parts by weight”.
[0028]
Synthesis of acrylic copolymer
Example 1
320 parts of 2-ethylhexyl acrylate, 80 parts of vinylpyrrolidone, 80 parts of hydroxyethyl acrylate, 20 parts of acrylic acid, and 300 parts of ethyl acetate are supplied to a separable flask equipped with a stirrer and a reflux condenser, and stirred and purged with nitrogen. Then, the temperature was raised to 75 ° C. A solution prepared by dissolving 2 parts of azobisisobrironitrile in 20 parts of ethyl acetate was divided into four parts, and one part thereof was added to a separable flask to initiate polymerization. The remaining 3 was added at 2 hour intervals from the second hour after the start of the reaction, and after the addition was completed, the reaction was further continued for 6 hours. After the start of the reaction for adjusting the viscosity, 50 parts of ethyl acetate were added four times every two hours. After the completion of the reaction, the mixture was cooled and then ethyl acetate was added to obtain a pressure-sensitive adhesive solution having a solid concentration of 30% by weight and a viscosity of 1.2 × 10 4 cps.
[0030]
Example 2-Example 7, Comparative Example 1-9
Polymerization was carried out in the same manner as in Example 1 except that the monomer composition in Example 1 was changed. Table 1 shows the monomer composition and viscosity.
Preparation of test sheet and measurement of displacement distance for displacement of shearing agent A plasticizer was added to the pressure-sensitive adhesive solution obtained in Example 1-7 and Comparative Example 1-9, and the whole liquid was uniformly dispersed with a dissolver. The mixture was stirred to obtain a mixture. The obtained mixed solution is applied on a silicon-treated PET film having a thickness of 35 μm so that the thickness of the adhesive layer after drying becomes 100 μm, dried, and then the adhesive layer is formed on a PET film having a thickness of 35 μm. Was laminated to obtain a pressure-sensitive adhesive sheet for skin. Next, the prepared sheet was cut into a tape having a width of 1 cm to form a tape. The sheet was vertically reciprocated with a load of 500 g with a bonding area of 1 cm × 1 cm at 25 ° C. and adhered to the bakelite plate. Min).
[0032]
Table 2 below shows the composition of the pressure-sensitive adhesive sheet for skin prepared and measured as described above, and the measurement results of the displacement distance.
Skin irritation test and sticking test
[Skin irritation test]
The following evaluations were performed on the test sheets obtained as described above, and the results are shown in Table 5.
Each test sheet (20 cm 2 ) was affixed to the upper arm of five adult males and peeled off after 24 hours. The state of the skin 1 hour after peeling was visually observed and evaluated according to the following evaluation criteria, and the average value of the sum of the scores of the five persons was used as an index.
(Evaluation criteria)
0: No erythema, 1: Very mild erythema barely discernable, 2: Evident erythema 3: Medium erythema, 4: Strong erythema of deep red
[Pasteability]
Each percutaneous absorption preparation was applied to the upper arm of five adult males, and peeled off 24 hours later. The state of attachment of the sheet on the skin immediately before peeling was visually observed and evaluated according to the following evaluation criteria.
(Evaluation criteria)
：: Almost all of them were completely affixed, □: Partial peeling of 1 to 3 persons, ×: Peeling of 4 to 5 persons
[Glue remaining test]
Each percutaneous absorption preparation was applied to the upper arm of five adult males, and peeled off 24 hours later. The state of the skin immediately after peeling was visually observed and evaluated according to the following evaluation criteria.
(Evaluation criteria)
○: Almost no glue residue, □: Partial glue residue for 1 to 3 people, ×: Glue residue for 4 to 5 people
Manufacture and evaluation of transdermal absorption preparations and cosmetic patches Acrylic alkyl ester compositions containing Examples 8-12 and Comparative Examples 19 and 20 and skin valuables were added as shown in Table 6. Prepared and evaluated a pharmaceutical patch and a cosmetic patch in the same manner as above. Table 6 shows the results. In the table, H represents indomethacin, K represents ketoprofen, and E represents vitamin E, respectively.
[0038]
Irritation A test piece (16 cm 2 in area) of a tape was applied to the depilated back of a Japanese white rabbit, and after 24 hours, the test piece was peeled off, and erythema on the skin immediately after peeling and 1 hour after peeling The condition was visually observed.
In this test, edema and crust formation were not observed. The number of repetitions was four for each formulation. The degree of erythema was evaluated according to the following five criteria of 0 to 4.
0: no erythema, 1: very slight erythema barely distinguishable, 2: evident erythema, 3: moderate erythema, 4: deep erythema.
The average value obtained by dividing the total score in each test by the number of repetitions was defined as the skin irritation index of each tape preparation.
[0039]
Sticking property The tape preparation was stuck to the skin of rabbits for 24 hours by the same operation as the above-mentioned irritation test, and the presence or absence of sticking property immediately before peeling was visually observed. The number of repetitions was four for each formulation. The evaluation criteria are as follows.
0: No peeling of the preparation 1: Partial peeling was observed 2: An average value (a value obtained by dividing the total of the evaluation points by the number of repetitions 4) that clearly observed the peeling was taken as the sticking index of each preparation.
The medical pressure-sensitive adhesive composition of the present invention and the percutaneously absorbable preparation and the cosmetic sheet using the same have the above-mentioned constitution, so that a good adhesion in which the adhesive force and the cohesive force are balanced can be obtained. Because of its properties, there is no adhesive residue when peeled off, and it is possible to reduce skin irritation caused by mechanical irritation such as damage to the stratum corneum on the skin surface and hair shaving.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002298052A JP2004097730A (en) | 2002-09-04 | 2002-09-04 | Medical adhesive composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002298052A JP2004097730A (en) | 2002-09-04 | 2002-09-04 | Medical adhesive composition |
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| Publication Number | Publication Date |
|---|---|
| JP2004097730A true JP2004097730A (en) | 2004-04-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002298052A Pending JP2004097730A (en) | 2002-09-04 | 2002-09-04 | Medical adhesive composition |
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| Country | Link |
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| JP (1) | JP2004097730A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005015537A (en) * | 2003-06-24 | 2005-01-20 | Saitama Daiichi Seiyaku Kk | Pressure-sensitive adhesive tape |
| JP2005015536A (en) * | 2003-06-24 | 2005-01-20 | Saitama Daiichi Seiyaku Kk | Pressure-sensitive adhesive tape |
| WO2006064747A1 (en) * | 2004-12-15 | 2006-06-22 | Saitama Daiichi Pharmaceutical Co., Ltd. | Medical tape preparation |
| JP2009029768A (en) * | 2007-07-24 | 2009-02-12 | Kosumedei Seiyaku Kk | Tape preparation for percutaneous absorption |
| EP2921540A1 (en) | 2014-03-18 | 2015-09-23 | Nitto Denko Corporation | Pressure-sensitive adhesive tape or sheet for application on skin |
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2002
- 2002-09-04 JP JP2002298052A patent/JP2004097730A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4527949B2 (en) * | 2003-06-24 | 2010-08-18 | ニプロパッチ株式会社 | Adhesive tape |
| JP2005015536A (en) * | 2003-06-24 | 2005-01-20 | Saitama Daiichi Seiyaku Kk | Pressure-sensitive adhesive tape |
| JP4589608B2 (en) * | 2003-06-24 | 2010-12-01 | ニプロパッチ株式会社 | Pressure sensitive adhesive tape |
| JP2005015537A (en) * | 2003-06-24 | 2005-01-20 | Saitama Daiichi Seiyaku Kk | Pressure-sensitive adhesive tape |
| JPWO2006064747A1 (en) * | 2004-12-15 | 2008-06-12 | 埼玉第一製薬株式会社 | Medical tape |
| WO2006064747A1 (en) * | 2004-12-15 | 2006-06-22 | Saitama Daiichi Pharmaceutical Co., Ltd. | Medical tape preparation |
| CN101080244B (en) * | 2004-12-15 | 2011-06-08 | 尼普洛外用药品株式会社 | Medical tape preparation |
| US7976865B2 (en) | 2004-12-15 | 2011-07-12 | Nipro Patch Co., Ltd. | Medical tape preparation |
| US8128946B2 (en) | 2004-12-15 | 2012-03-06 | Nipro Patch Co., Ltd. | Medical tape preparation |
| JP5016309B2 (en) * | 2004-12-15 | 2012-09-05 | ニプロパッチ株式会社 | Medical tape |
| KR101242834B1 (en) | 2004-12-15 | 2013-03-12 | 니프로 패치 가부시키가이샤 | Medical tape preparation |
| JP2009029768A (en) * | 2007-07-24 | 2009-02-12 | Kosumedei Seiyaku Kk | Tape preparation for percutaneous absorption |
| EP2921540A1 (en) | 2014-03-18 | 2015-09-23 | Nitto Denko Corporation | Pressure-sensitive adhesive tape or sheet for application on skin |
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